Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control. (November 2022)

• Record Type: Journal Article
• Authors: Chen, Guanqun; Harwood, John L.; Lemieux, M. Joanne; Stone, Scot J.; Weselake, Randall J.
• Is Part Of: Progress in lipid research. Volume 88(2022)
• Publication Date: 2022-11
• Subjects: Diacylglycerol acyltransferase -- Storage lipid -- Triacylglycerol -- Lipid biotechnology -- Storage lipid biosynthesis -- Lipid metabolic disorders; ABA abscisic acid -- ABI ABSCISIC ACID INSENSITIVE -- ACAT acyl-CoA:cholesterol acyltransferase -- ACBP acyl-CoA binding protein -- ACCase acetyl-CoA carboxylase -- ACP acyl carrier protein -- ACS Acetyl-CoA synthetase -- acyl-P acyl-phosphate -- AP2/EREBP APETALA2-ethylene responsive element-binding protein -- ARA arachidonic acid -- ARE acyl-CoA:cholesterol acyltransferase-related enzyme -- AUERO1 Aureochrome-1 -- BCCP BIOTIN CARBOXYL CARRIER PROTEIN -- bHLH a basic helix-loop-helix TF -- BiFC bimolecular fluorescent complementation -- BTA betaine synthase -- bZIP a basic leucine zipper-domain containing TF -- CBL cocoa butter-like lipid -- CCT CTP:phosphocholine cytidylyltransferase -- Core HCV capsid protein -- CPM 7-diethylaminl-3-(4'-maleimidyl-phenyl)-4-methylcoumarin -- CPT CDP-choline:1, 2-diacylglycerol cholinephosphotransferase -- CoA coenzyme A -- cryo-EM cryo-electron microscopy -- DAG 1, 2-diacyl-sn-glycerol -- DAcT diacylglycerol acetyltransferase -- DBTL design/build/test/learn -- DCR defective in cuticular ridges -- DGAT acyl-CoA:diacylglycerol acyltransferase -- DGD digalactosyldiacylglycerol synthase -- DGDG digalactosyldiacylglycerol -- DGTS diacylglyceryl-3-O-4′-(N, N, N-trimethyl)-homoserine -- DHA docosahexaenoic acid -- DHAP dihydroxyacetone phosphate -- Dof-type TF DNA binding with one finger type TF -- DTNB 5, 5'-dithiobis(2-nitro benzoic acid) -- DW dry weight -- DYRK dual-specificity tyrosine phosphorylation-regulated kinase -- ENR enoyl-ACP reductase -- EPA eicosapentaenoic acid -- ER endoplasmic reticulum -- ESI electrospray ionization -- FA fatty acid -- FAD fatty acid desaturase -- FAE FATTY ACID ELONGATION -- FAEE fatty acid ethyl ester -- FAH fatty acid hydroxylase -- FALDR fatty aldehyde reductase -- FAME fatty acid methyl ester -- FAR fatty acyl reductase -- FatA/B fatty acid thioesterase A/B -- FAX1 fatty acid export 1 -- FCS familial chylomicronemia syndrome -- FID flame ionization detection -- FFA free fatty acid -- GBSS1 granule-bound starch synthase1 -- GC gas chromatography -- GPAT acyl-CoA:sn-glycerol-3-phosphate acyltransferase -- GPDH sn-glycerol-3-phosphate dehydrogenase -- GRAS generally recognized as safe -- G3P sn-glycerol-3-phosphate -- HAD hydroxyacyl-ACP dehydrase -- HCV hepatitis C virus -- HDL high-density lipoprotein -- HTP high-throughput -- i autoinhibitory motif -- IDR intrinsically disordered region -- IM intramuscular -- KAR ketoacyl-ACP reductase -- KAS keto-acyl-CoA synthase -- LACS long-chain acyl-CoA synthetase -- LC liquid chromatography -- LD lipid droplet -- LEC LEAFY COTYLEDON -- LPA lysophosphatidic acid -- LPAAT acyl-CoA:lysophosphatidic acid acyltransferase -- LPC lysophosphatidylcholine -- LPCAT acyl-CoA:lysophosphatidylcholine acyltransferase -- LPE lysophosphatidylethanolamine -- LPL lysophospholipid -- MAG monoacylglycerol -- MBOAT membrane-bound O-acyltransferase -- MCA Metabolic Control Analysis -- MCMT malonyl-CoA:ACP malonyltransferase -- ME metabolic engineering -- MGAT acyl-CoA:monoacylglycerol acyltransferase -- MGD monogalactosyldiacylglycerol synthase -- MGDG monogalactosyldiacylglycerol -- MS mass spectrometry -- NBD N-[(7-nitro-2-1, 3-benzoxadiazol-4-yl)-methyl]amino -- NAFLD non-alcoholic fatty liver disease -- NE non-esterified -- NPL non-polar lipid -- NRP1 pathogenesis-related genes 1 -- NTD N-terminal domain -- PA phosphatidic acid -- PAP phosphatidic acid phosphatase -- PC phosphatidylcholine -- PCholine phosphocholine -- PDAT phospholipid:diacylglycerol acyltransferase -- PDCT phosphatidylcholine:diacylglycerol cholinephosphotransferase -- PDH pyruvate dehydrogenase complex -- PE phosphatidylethanolamine -- PEG polyethylene glycol -- PES phytyl ester synthase -- PG phosphatidylglycerol -- PGD1 plastid galactoglycerolipid degradation 1 -- Pi inorganic phosphate -- PL phospholipid -- PLA2 phospholipase A2 -- PSR1 Pi starvation response 1 -- PUFA polyunsaturated fatty acid -- PXA1 peroxisomal membrane transporter1 -- QTL quantitative trait locus -- SAD stearoyl-ACP desaturase -- SCD stearoyl-CoA desaturase -- SDP1 SUGAR-DEPENDENT1 -- SE steryl ester -- SFR2 SENSITIVE TO FREEZING2 -- SNP single nucleotide polymorphism -- SnRK1 sucrose non-fermenting-1-related kinase -- SPA scintillation proximity assay -- SQD sulfoquinovosyldiacylglycerol synthase -- SQDG sulfoquinovosyldiacylglycerol -- SUC2 suc-proton symporter 2 -- TAG triacylglycerol -- TAR1 tryptophan aminotransferase-related protein 1 -- TF transcription factor -- TGD trigalactosyldiacylglycerol -- TLC thin layer chromatography -- TMD transmembrane domain -- TORC1 Target of Rapamycin complex 1 -- WE wax ester -- WIN1 WAX INDUCER1/SHINE1 -- WRI WRINKLED -- WS wax ester synthase -- WSD bifunctional wax ester synthase-diacylglycerol acyltransferase -- WT wild type -- VLCFA very-long-chain fatty acid -- VLDL very low-density lipoprotein -- 3-D three-dimensional.; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2022.101181
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: Acyl-CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the last reaction in the acyl-CoA-dependent biosynthesis of triacylglycerol (TAG). DGAT activity resides mainly in DGAT1 and DGAT2 in eukaryotes and bifunctional wax ester synthase-diacylglycerol acyltransferase (WSD) in bacteria, which are all membrane-bound proteins but exhibit no sequence homology to each other. Recent studies also identified other DGAT enzymes such as the soluble DGAT3 and diacylglycerol acetyltransferase (EaDAcT), as well as enzymes with DGAT activities including defective in cuticular ridges (DCR) and steryl and phytyl ester synthases (PESs). This review comprehensively discusses research advances on DGATs in prokaryotes and eukaryotes with a focus on their biochemical properties, physiological roles, and biotechnological and therapeutic applications. The review begins with a discussion of DGAT assay methods, followed by a systematic discussion of TAG biosynthesis and the properties and physiological role of DGATs. Thereafter, the review discusses the three-dimensional structure and insights into mechanism of action of human DGAT1, and the modeled DGAT1 from Brassica napus . The review then examines metabolic engineering strategies involving manipulation of DGAT, followed by a discussion of its therapeutic applications. DGAT in relation to improvement of traits of farmed animals is also discussed along with DGATs in various other eukaryotic organisms.